OP0131 DISEASE ACTIVITY-GUIDED DOSE OPTIMIZATION INCLUDING DISCONTINUATION OF TNF-INHIBITORS IN RHEUMATOID ARTHRITIS IS EFFECTIVE FOR UP TO 10 YEARS: RESULTS OF THE DRESS STUDY
Authors: C. Van der Togt, N. Den Broeder, A. Van der Maas, A. Den Broeder, N. Van Herwaarden
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Tumor necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA) but have their drawbacks such as the need for self-injection, infections and costs. To reduce these disadvantages, disease activity-guided dose optimization (DAGDO) has shown to be an effective and safe strategy.[1] During DAGDO, a stepwise dose reduction of the TNFi is performed if allowed by the disease activity. In the Dose Reduction Strategy of Subcutaneous TNFi (DRESS) study, effectiveness and safety of DAGDO has been shown in RA patients for up to three years.[2, 3] However, long term outcomes of DAGDO are scarce, and it is debated whether a discontinuation attempt should be included. <h3>Objectives</h3> To assess 10-year effectiveness of DAGDO of TNFi in the DRESS cohort, specifically 1) disease activity over time, 2) biological and targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) dose over time, 3) proportion of patients with a DAGDO attempt, and 4) proportion of patients with a discontinuation attempt and duration of b/tsDMARD discontinuation. <h3>Methods</h3> Observational follow-up (starting from DRESS baseline) of patients who completed the 3-year DRESS extension. During the DRESS intervention phase (month 0-18), RA patients were randomized to DAGDO or continuation of TNFi (adalimumab or etanercept), but thereafter, DAGDO was allowed for all patients. The DAGDO protocol contained the following steps, displayed as a percentage of the current daily dose to the defined daily dose (DDD): 100%-66%-50%-(33%)-0% (full discontinuation). The disease activity was operationalized as the mean time-weighted (MTW) DAS28-CRP. The specific DRESS TNFi and all b/tsDMARD dose over time were displayed as the MTW dose per year in %DDD. The duration of b/tsDMARD discontinuation was analyzed using the time between discontinuation and restart of the same or another b/tsDMARD, or censoring. <h3>Results</h3> 170 patients (of the original 180) could be included in the study (Table 1). The median follow-up time was 10.0 years (IQR 9.3-10.3) and the MTW DAS28-CRP during the whole period 2.13 (95% CI 2.10-2.16) (Figure 1). The DRESS TNFi dose decreased from 97% at baseline (95% CI 96%-99%) to 49% at year 5 (95% CI 42%-56%) and remained stable thereafter (Figure 1). The dose of any b/tsDMARD was comparable although slightly higher. Of the 161 patients with ≥1 DAGDO attempt of their DRESS TNFi during the study, 119 (74%, 95% CI 66%-80%) tapered until full discontinuation. The median time from discontinuation to restart of the first discontinuation attempt was 8 months (IQR 3 – 45 months), and 25 patients (21%, 95% CI 14%-29%) never had to restart their TNFi or another b/tsDMARD throughout the study. <h3>Conclusion</h3> In this 10-year TNFi dose optimization study, we found a stable low disease activity and halved TNFi dose. The inclusion of discontinuation in DAGDO does not seem to cause disease deterioration and b/tsDMARD free remission for a relevant period of time is possible in a non-negligible number of patients. Overall, this study shows effectiveness of DAGDO of TNFi in RA up to 10 years. <h3>References</h3> [1] Verhoef et al., Cochrane Database Syst Rev. 2019 May 24;5(5):CD010455. [2] van Herwaarden et al., BMJ. 2015 Apr 9;350:h1389. [3] Bouman et al., Ann Rheum Dis. 2017 Oct;76(10):1716-1722. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Celeste van der Togt: None declared, Nathan den Broeder: None declared, Aatke van der Maas: None declared, Alfons den Broeder Grant/research support from: Grants to the institution from abbvie, gilead, pfizer, novartis, lilly, galapagos, sanofi, Noortje van Herwaarden: None declared.